Antibodies are proteins that bind a specific antigen. Generally, antibodies are specific for their targets, have the ability to mediate immune effector mechanisms, and have a long half-life in serum. Such properties make antibodies powerful therapeutics. Monoclonal antibodies are used therapeutically for the treatment of a variety of conditions including cancer, inflammation, and other diseases. There are currently over two dozen therapeutic antibody products on the market and hundreds in development. There is a constant need for new antibodies having desirable properties and methods for isolating the same.
It is understood that an the full antibody repertoire of an immunized subject (also referred as “immunized antibody repertoire” or “immunized repertoire”) contains a very large number of antibodies having sequence diversity which can, in some cases, impart variations with respect to affinity, specificity and in vivo functionality. In view of this it is sometimes desirable to sample a significant number of antibodies from a subject to identify antibodies that possess similar or improved properties relative to, e.g., an antibody of interest. Therefore there is a need in the art for the identification of new antibodies in a direct and efficient manner for use in the development of therapeutic candidates, in diagnostic applications and/or research products.
US20110065112 describes a method for identifying lineage-related antibodies. In some embodiments this method involves: obtaining the antibody sequences from a population of B cells; grouping the antibody sequences to provide a plurality of groups of lineage-related antibodies; testing a single antibody from each of the groups in a bioassay and, after the first antibody has been identified, testing further antibodies that are in the same group as the first antibody in a second bioassay. US20110065112 also describes a method that involves testing a plurality of antibodies obtained from a first portion of an antibody producing organ of an animal; obtaining the sequence of a first identified antibody; obtaining from a second portion of said antibody producing organ the sequences of further antibodies that are related by lineage to said first antibody; and, c) testing the further antibodies in a second bioassay.
US20100204059 describes a method for obtaining nucleic acid encoding a plurality of antibodies. In certain embodiments, the method comprises obtaining from an immunized animal nucleic acid encoding the amino acid sequence of the heavy and light chains of a second antibody that binds to the antigen as a first antibody and differs in amino acid sequence to the first antibody, wherein the obtaining is done by amplification using: i. a first primer pair that includes oligonucleotides are complementary to CDR-encoding regions first antibody.
The inventors have developed a new method that serves to identify lineage-related antibodies from an antibody repertoire of an immunized animal, based on the properties of an antibody of interest using computational means.